Regulation of Akt during hibernation in Richardson's ground squirrels
Regulation of Akt during hibernation in Richardson's ground squirrels
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DOI：
10.1016/j.bbagen.2007.10.009
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发表时间：
2008-02-01
影响因子：
3
通讯作者：
Storey, Kenneth B.
中科院分区：
文献类型：
--
作者：
Abnous, Khalil;Dieni, Christopher A.;Storey, Kenneth B.
Akt（或蛋白激酶B）在协调细胞生长、存活和抗凋亡反应中起着核心作用，我们假设Akt活性和性质的变化将有助于哺乳动物冬眠期间发生的代谢功能的重新优先化。Akt在理查森的地面松鼠，黄鼠的骨骼肌和肝脏进行了分析，比较从常温和冬眠状态的酶。Akt活性，用合成肽底物测量，在冬眠期间两个器官中下降了60-65%。蛋白质印迹法表明，总Akt蛋白没有改变冬眠，但活性，磷酸化Akt（Ser 473）减少了40%，在肌肉中相比，常温控制，几乎检测不到在肝脏中。肌肉Akt的动力学分析表明，Akt肽的S-0.5值在冬眠期间降低了28%，而S-0.5 ATP增加了330%。在10 ℃下的测定也使常温Akt的S-0.5 ATP升高了350%。ATP亲和力的变化将限制Akt在冬眠动物中的功能，因为肌肉腺苷酸池的大小在冷麻痹期间也被强烈抑制。AKT的其他参数是相同的，包括从Arrhenius图计算的活化能和对尿素变性的敏感性。肌肉提取物的DEAE-Sephadex层析显示，Akt活性在低温下有三个峰，但在冬眠期间只有两个峰，这表明同工酶在冬眠期间差异去磷酸化。改变的酶特性和Akt活性的抑制将有助于协调抑制能量昂贵的合成代谢和生长过程，这是在数周的冬季休眠期间保持活力所必需的。(C)2007 Elsevier B. V.保留所有权利。
Akt (or protein kinase B) plays a central role in coordinating growth, survival and anti-apoptotic responses in cells and we hypothesized that changes in Akt activity and properties would aid the reprioritization of metabolic functions that occurs during mammalian hibernation. Akt was analyzed in skeletal muscle and liver of Richardson's ground squirrels, Spermophilus richardsonii, comparing the enzyme from euthermic and hibernating states. Akt activity, measured with a synthetic peptide substrate, decreased by 60-65% in both organs during hibernation. Western blotting showed that total Akt protein did not change in hibernation but active, phosphorylated Akt (Ser 473) was reduced by 40% in muscle compared with euthermic controls and was almost undetectable in liver. Kinetic analysis of muscle Akt showed that S-0.5 values for Akt peptide were 28% lower during hibernation, compared with the euthermic enzyme, whereas S-0.5 ATP increased by 330%. Assay at 10 degrees C also elevated S-0.5 ATP of euthermic Akt by 350%. Changes in ATP affinity would limit Akt function in the hibernator since the muscle adenylate pool size is also strongly suppressed during cold torpor. Other parameters of euthermic and hibernator Akt were the same including activation energy calculated from Arrhenius plots and sensitivity to urea denaturation. DEAE Sephadex chromatography of muscle extracts revealed three peaks of Akt activity in euthermia, but only two during hibernation suggesting isozymes are differentially dephosphorylated during torpor. Altered enzyme properties and suppression of Akt activity would contribute to the coordinated suppression of energy-expensive anabolic and growth processes that is needed to maintain viability during over weeks of winter torpor. (C) 2007 Elsevier B.V. All rights reserved.